Spatial expression of germ cell markers during maturation of human fetal male gonads: an immunohistochemical study

The aim of the present study was to examine fetal male germ cells for expression of proteins associated with differentiation and maturation and to compare them with morphologically defined subpopulations.

Testes of 61 fetuses from week 12 of gestation to the newborn period were selected. Immunohistochemistry was performed using antibodies to proteins associated with differentiation of germ cells (c-KIT, AP-2gamma) or pluripotency (OCT3/4), oncofetal protein M2A and spermatogonial marker MAGE-A4.

Two subtypes of fetal germ cells were detected by quantification and immunohistochemistry. Nearly all germ cells with morphological criteria of gonocytes and intermediate cells co-expressed OCT3/4, c-KIT, M2A and AP-2gamma. Starting from week 12, their number increased up to week 18/19 and then declined continuously during further development. After week 25, pre-spermatogonia were predominant and expressed MAGE-A4 selectively.

Fetal male germ cells are comprised of two major groups with distinct immunohistochemical phenotypes. Germ cells that are predominantly found before week 25 of gestation co-express oncofetal proteins OCT3/4, c-KIT, M2A and AP-2gamma. After week 25, most germ cells have lost their pluripotent potential and acquire a spermatogonial phenotype defined by expression of MAGE-A4.